A Study of Baricitinib and Simvastatin in Healthy Participants

Effects of Multiple Baricitinib (LY3009104) Doses on the Pharmacokinetics of a Cytochrome P450 3A Substrate, Simvastatin, in Healthy Subjects

The purposes of this study are to determine the effects of baricitinib on the time it takes to remove simvastatin from the body and to look at how well-tolerated and safe baricitinib is when given alone and in combination with simvastatin. Side effects will be documented. The study will last approximately 7 days from the first dose to the end of the study (not including screening or follow-up).

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Baricitinib; Drug: Simvastatin

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS2 9LH
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male participants - Agree to use 2 reliable methods of birth control with female partners of childbearing potential during the study and for at least 3 months following the last dose of study drug
• Female participants - Women not of childbearing potential due to surgical sterilization confirmed by medical history, or menopause
• Have a body mass index of 18.0 to 29.0 kilograms per meter squared (kg/m^2), inclusive
• Have clinical laboratory test results within the normal reference range
• Have normal renal function
• Have normal blood pressure and pulse rate

Exclusion Criteria:

• Are currently enrolled in a clinical trial involving a study drug or off-label use of a drug or device, or are concurrently enrolled in any other type of medical research
• Have completed or discontinued within the last 90 days from a clinical trial involving a study drug
• Have previously completed or withdrawn from this study or any other study investigating baricitinib, and have previously received baricitinib
• Have known allergies to baricitinib, simvastatin, related compounds, or any components of the baricitinib or simvastatin formulations, or history of significant atopy
• Have an abnormality in the 12-lead electrocardiogram (ECG)
• Have a history of, or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (including hypothyroidism), hematological, or neurological disorders
• Have current or recent history of myalgia or muscle weakness
• Regularly use known drugs of abuse and/or show positive findings on urinary drug screening
• Have a current or recent history of a clinically significant bacterial, fungal, parasitic, viral (not including rhinopharyngitis), or mycobacterial infection
• Have had symptomatic herpes zoster or herpes simplex infection within 90 days prior to the first dose
• Have an absolute neutrophil count (ANC) less than 2 × 10^9/liters (L) [2000 cells/microliter (μL)] at screening or day prior to first dose of study drug. For abnormal values, a single repeat will be allowed
• Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies
• Show evidence of hepatitis C infection and/or positive hepatitis C antibody
• Show evidence of hepatitis B infection and/or positive hepatitis B surface antigen
• Are women who are lactating
• Have been exposed to a live vaccine within 12 weeks prior to the first dose or expected to need/receive a live vaccine (including herpes zoster vaccination) during the course of the study
• Intend to use over-the-counter or prescription medication (including salicylate drugs) and/or herbal supplements within 14 days prior to dosing and during the study or intended use of vitamin supplements from Day 1 until discharge from the Clinical Research Unit (CRU)
• Have consumed or intend to consume grapefruit or grapefruit-containing products within 14 days prior to the first dose and throughout the study
• Have donated or lost blood of more than 500 milliliters (mL) within the last 3 months
• Have an average weekly alcohol intake that exceeds 28 units per week (males) and 21 units per week (females), or are unwilling to stop alcohol consumption from 48 hours prior to the first dose until discharge from the CRU at the end of Period 2
• History of, in the opinion of the investigator, excessive methylxanthine use within the previous 6 months, such as greater than (>)6 cups of coffee (or equivalent) per day
• Currently smoke more than 10 cigarettes per day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Simvastatin; Single oral dose of 40 milligrams (mg) simvastatin on Day 1.	Drug: Simvastatin; Administered orally
Experimental: Baricitinib + Simvastatin; Oral doses of 10 mg baricitinib once daily (QD) on Days 3 to 7, with a single oral dose of 40 mg simvastatin coadministered on Day 6.	Drug: Baricitinib; Administered orally; Other Names: LY3009104; Drug: Simvastatin; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Simvastatin and Simvastatin Acid	The Cmax of simvastatin [a cytochrome P450 (CYP) 3A substrate] and its active acid metabolite (simvastatin acid) is reported.	Period 1, Day 1 and Period 2, Day 6: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours postdose
PK: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] of Simvastatin and Simvastatin Acid	The AUC(0-∞) of simvastatin (a CYP3A substrate) and its active acid metabolite (simvastatin acid) is reported.	Period 1, Day 1 and Period 2, Day 6: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours postdose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: October 8, 2013
• First Submitted That Met QC Criteria: October 8, 2013
• First Posted (Estimate): October 10, 2013

Study Record Updates

• Last Update Posted (Actual): June 6, 2017
• Last Update Submitted That Met QC Criteria: May 15, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: 14606; I4V-MC-JAGI (Other Identifier: Eli Lilly and Company)